Bone marrow-derived B lymphocytes mediate the humoral immune response. The B cell differentiation pathway can be divided into two stages based upon contact with antigen. Unprimed B lymphocytes are derived from virgin B cells which develop from multipotent stem cells. Memory B cells are generated as a result of antigenic stimulation. While the unprimed B lymphocytes acting as IgM antibody forming cell progenitors and the memory B cells giving an IgG antibody forming cell response have been well characterized, the identity of the precursors of the memory cell is unknown. The physical characteristics of the precursor of the memory B lymphocyte will be determined and the cells isolated by a battery of cell separation procedures, based upon size, density, and surface charge. Immunoglobulin isotype, differentiation antigens, and nonimmunoglobulin surface receptors will also be used to characterize the memory B cell precursor. The various B cell subpopulations separated by these methods will be assayed for their ability to generate a memory state in response to antigenic priming and subsequently mount a memory response following secondary challenge. A long-term adoptive assay based upon the use of allotype congenic mice will allow the enumeration of a donor IgG response in the presence of a significant host contribution. Additional parameters will be investigated, including kinetics of memory generation, turnover rate of the precursor cell, and relationship between the memory precursors and the cells giving a primary antibody response.